Long Term Goal: To develop EMB-001 for the treatment of cocaine dependence. Background: Cocaine dependence and abuse afflict 1.6 million people in the U.S. and are associated with enormous costs to individuals and to the overall society. There are currently no medications approved for the treatment of cocaine dependence, and there is a compelling need for safe and effective therapeutics to treat this serious condition. The Louisiana State University Health Sciences Center in Shreveport (LSUHSC-S) and Embera NeuroTherapeutics are developing EMB-001 for the treatment of cocaine addiction. EMB-001 is a combination drug product comprising two FDA-approved medications, the benzodiazepine oxazepam and the cortisol synthesis inhibitor metyrapone. The development of this new medication emerged from 20 years of NIH-funded research into the role of stress and the hypothalamo-pituitary-adrenal (HPA) axis in addiction. EMB-001 has already been demonstrated to be effective in multiple animal models of cocaine addiction and in a pilot clinical trial carried out using the commercially available single agent drugs in cocaine-dependent patients. This proposal is aimed at continuing the development of this promising therapeutic and advancing the combination drug product into clinical testing. The Specific Aims are as follows: Specific Aim 1: To complete the development and manufacture of EMB-001. Specific Aim 2: To complete the preclinical pharmacology and toxicology studies needed to support an IND submission. Specific Aim 3: To complete a Phase 1 clinical trial of EMB-001. At the completion of the funding period, we will be prepared to evaluate EMB-001 in Phase 2 safety and efficacy studies in cocaine-dependent subjects. PUBLIC HEALTH RELEVANCE: This proposal is focused on the development of EMB-001, a novel combination drug product for the treatment of cocaine addiction. The goal of the work is to advance EMB-001 through a Phase 1 clinical trial.